4-30721921-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001173523.2(PCDH7):c.499G>T(p.Ala167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000445 in 1,572,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
PCDH7
NM_001173523.2 missense
NM_001173523.2 missense
Scores
4
13
2
Clinical Significance
Conservation
PhyloP100: 6.66
Genes affected
PCDH7 (HGNC:8659): (protocadherin 7) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes a protein with an extracellular domain containing 7 cadherin repeats. The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.933
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH7 | NM_001173523.2 | c.499G>T | p.Ala167Ser | missense_variant | 1/3 | ENST00000695919.1 | |
PCDH7 | NM_032457.4 | c.499G>T | p.Ala167Ser | missense_variant | 1/3 | ||
PCDH7 | NM_002589.4 | c.499G>T | p.Ala167Ser | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH7 | ENST00000695919.1 | c.499G>T | p.Ala167Ser | missense_variant | 1/3 | NM_001173523.2 | A1 | ||
ENST00000660555.1 | n.50C>A | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000223 AC: 4AN: 178982Hom.: 0 AF XY: 0.0000102 AC XY: 1AN XY: 97584
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GnomAD4 exome AF: 0.00000352 AC: 5AN: 1420468Hom.: 0 Cov.: 32 AF XY: 0.00000284 AC XY: 2AN XY: 703684
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74282
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 15, 2021 | The c.499G>T (p.A167S) alteration is located in exon 1 (coding exon 1) of the PCDH7 gene. This alteration results from a G to T substitution at nucleotide position 499, causing the alanine (A) at amino acid position 167 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of glycosylation at A167 (P = 0.0142);Gain of glycosylation at A167 (P = 0.0142);
MVP
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at